Cloning and transcriptional regulation of genes responsible for synthesis of gangliosides

Guichao Zeng, Robert K Yu

Research output: Contribution to journalReview article

17 Scopus citations

Abstract

Ganglioside synthases are glycosyltransferases involved in the biosynthesis of glycoconjugates. A number of ganglioside synthase genes have been cloned and characterized. They are classified into different families of glycosyl-transferases based on similarities of their amino acid sequences. Tissue-specific expression of these genes has been analyzed by hybridization using cDNA fragments. Enzymatic characterization with the expressed recombinant enzymes showed these enzymes differ in their donor and acceptor substrate specificities and other biochemical parameters. In vitro enzymatic analysis also showed that one linkage can be synthesized by multiple enzymes and one enzyme may be responsible for synthesis of multiple gangliosides. Following the cloning of the ganglioside synthase genes, the promoters of the key synthase genes in the ganglioside biosynthetic pathway have been cloned and analyzed. All of thd promoters are TATA-less, lacking a CCAAT box but containing GC-rich boxes, characteristic of the house-keeping genes, although transcription of ganglioside synthase genes is subject to complex developmental and tissue-specific regulation. A set of cis-acting elements and transcription factors, including Sp1, AP2, and CREB, function in the proximal promoters, Negative-regulatory regions have also been defined in most of the promoters. We present here an overview of these genes and their transcriptional regulation.

Original languageEnglish (US)
Pages (from-to)317-324
Number of pages8
JournalCurrent Drug Targets
Volume9
Issue number4
DOIs
StatePublished - Apr 1 2008

Keywords

  • Ganglioside
  • Ganglioside synthase
  • Gene cloning
  • Glycosyltransferase
  • Transcription factors
  • Transcription regulation

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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